tbuckley/cabot-search huggingface dataset:
Cost-effectiveness of MRE versus VCTE in staging fibrosis for nonalcoholic fatty liver disease (NAFLD) patients with advanced fibrosis
Authors: Kinpritma Sangha, Stephanie T. Chang, Ramsey Cheung, Vibhas S. Deshpande
Journal: Hepatology (2023)

NAFLD is a common cause of liver disease. To determine the optimal testing strategy for NAFLD patients with advanced fibrosis, several factors such as diagnostic accuracy, failure rates, costs of examinations, and potential treatment options need to be considered. The purpose of this study was to determine the cost-effectiveness of combination testing involving vibration-controlled transient elastography (VCTE) versus magnetic resonance elastography (MRE) as a frontline imaging strategy for NAFLD patients with advanced fibrosis.A Markov model was developed from the US perspective. The base-case scenario in this model included patients aged 50 years with a Fibrosis-4 score of ≥2.67 and suspected advanced fibrosis. The model included a decision tree and a Markov state-transition model including 5 health states: fibrosis stage 1-2, advanced fibrosis, compensated cirrhosis, decompensated cirrhosis, and death. Both deterministic and probabilistic sensitivity analyses were performed.Staging fibrosis with MRE cost $8388 more than VCTE but led to an additional 1.19 Quality-adjusted life years (QALYs) with the incremental cost-effectiveness ratio of $7048/QALY. The cost-effectiveness analysis of the 5 strategies revealed that MRE+biopsy and VCTE+MRE+biopsy were the most cost-effective with the incremental cost-effectiveness ratios of $8054/QALY and $8241/QALY, respectively. Furthermore, sensitivity analyses indicated that MRE remained cost-effective with a sensitivity of ≥0.77, whereas VCTE became cost-effective with a sensitivity of ≥0.82.MRE was not only cost-effective than VCTE as the frontline modality for staging NAFLD patients with Fibrosis-4 ≥2.67 with incremental cost-effectiveness ratio of $7048/QALY but also remained cost-effective when used as a follow-up in instances of VCTE failure to diagnose.
Longitudinal Trends in Suicidal Thoughts and Behaviors Among US Military Veterans During the COVID-19 Pandemic
Authors: Ian C. Fischer, Brandon Nichter, Peter J. Na, Sonya B. Norman, John H. Krystal, Robert H. Pietrzak
Journal: JAMA Psychiatry (2023)

Importance Concerns have been raised since the onset of the COVID-19 pandemic that vulnerable populations, such as military veterans, may be at increased risk of suicidal thoughts and behaviors (STBs). Objective To examine longitudinal trends in STBs in US military veterans during the first 3 years of the COVID-19 pandemic. Design, Setting, and Participants This cohort study is a population-based longitudinal study including US military veterans that used 3 surveys from the National Health and Resilience in Veterans Study. Median dates of data collection were November 21, 2019 (prepandemic); November 14, 2020; and August 18, 2022. Main Outcomes and Measures Lifetime and past-year suicidal ideation, suicide planning, and suicide attempt. Results In this longitudinal study including 2441 veterans (mean [SD] age, 63.2 years [14.0]; 2182 [92.1%] male), past-year suicidal ideation decreased from 9.3% prepandemic (95% CI, 8.2%-10.6%) to 6.8% a year later (95% CI%, 5.8-7.9%) and then slightly increased to 7.7% (95% CI, 6.7%-8.9%) 2 years later. In total, 9 veterans (0.4%) reported attempting suicide at least once during the follow-up period, while 100 (3.8%) developed new-onset suicidal ideation and 28 (1.2%) developed new-onset suicide planning. After adjusting for sociodemographic and military characteristics, factors strongly associated with new-onset suicidal ideation included higher education (odds ratio [OR], 3.27; 95% CI, 1.95-5.46), lifetime substance use disorder (OR, 2.07; 95% CI, 1.23-3.46), prepandemic loneliness (OR, 1.28; 95% CI, 1.09-1.49), and lower prepandemic purpose in life (OR, 0.92; 95% CI, 0.86-0.97). Factors associated with new-onset suicide planning included lifetime substance use disorder (OR, 3.03; 95% CI, 1.22-7.55), higher prepandemic psychiatric distress (OR, 1.52; 95% CI, 1.06-2.18), and lower prepandemic purpose in life (OR, 0.88; 95% CI, 0.81-0.95). Conclusions and Relevance Contrary to expectations, the prevalence of STBs did not increase for most US veterans during the COVID-19 pandemic. However, veterans with preexisting loneliness, psychiatric distress, and lower purpose in life were at heightened risk of developing new-onset suicidal ideation and suicide planning during the pandemic. Evidence-based prevention and intervention efforts that target these factors may help mitigate suicide risk in this population.
Children's interactions with virtual assistants: Moving beyond depictions of social agents
Authors: Lauren N. Girouard-Hallam, Judith H. Danovitch
Journal: Behavioral and Brain Sciences (2023)

Abstract Clark and Fischer argue that people see social robots as depictions of social agents. However, people's interactions with virtual assistants may change their beliefs about social robots. Children and adults with exposure to virtual assistants may view social robots not as depictions of social agents, but as social agents belonging to a unique ontological category.
Unpredictable robots elicit responsibility attributions
Authors: Matija Franklin, Edmond Awad, Hal Ashton, David Lagnado
Journal: Behavioral and Brain Sciences (2023)

Abstract Do people hold robots responsible for their actions? While Clark and Fischer present a useful framework for interpreting social robots, we argue that they fail to account for people's willingness to assign responsibility to robots in certain contexts, such as when a robot performs actions not predictable by its user or programmer.
Patient Perspectives of Health System Barriers to Accessing Care for Hidradenitis Suppurativa
Authors: Leandra A. Barnes, Neha Shukla, Maia Paul, Isabella de Vere Hunt, Meghan C. Halley, Eleni Linos, Haley B. Naik
Journal: JAMA Dermatology (2023)

Patient-perceived barriers to hidradenitis suppurativa (HS) care are poorly understood. Understanding health care barriers is a critical first step toward improving care for this population.
How deep is AI's love? Understanding relational AI
Authors: Omri Gillath, Syed Abumusab, Ting Ai, Michael S. Branicky, Robert B. Davison, Maxwell Rulo, John Symons, Gregory Thomas
Journal: Behavioral and Brain Sciences (2023)

Abstract We suggest that as people move to construe robots as social agents, interact with them, and treat them as capable of social ties, they might develop (close) relationships with them. We then ask what kind of relationships can people form with bots, what functions can bots fulfill, and what are the societal and moral implications of such relationships.
Associations of Changes in Sleep and Emotional and Behavioral Problems From Late Childhood to Early Adolescence
Authors: Rebecca Cooper, Maria A. Di Biase, Bei Bei, Jon Quach, Vanessa Cropley
Journal: JAMA Psychiatry (2023)

Sleep problems and psychopathology symptoms are highly comorbid and bidirectionally correlated across childhood and adolescence. Whether these associations are specific to discrete profiles of sleep problems and specific internalizing and externalizing phenomena is currently unclear.
Microsatellite instability in noncolorectal and nonendometrial malignancies in patients with Lynch syndrome
Authors: Lisa Elze, Rachel S van der Post, Janet R Vos, Arjen R Mensenkamp, Mirjam S C de Hullu, Iris D Nagtegaal, Nicoline Hoogerbrugge, Richarda M de Voer, Marjolijn J L Ligtenberg
Journal: JNCI Journal of the National Cancer Institute (2023)

Individuals with Lynch syndrome are at increased hereditary risk of colorectal and endometrial carcinomas with microsatellite instability (MSI-H) and mismatch repair-deficiency (dMMR), which make these tumors vulnerable to therapy with immune checkpoint inhibitors. Our aim is to assess how often other tumor types in these individuals share these characteristics.We retrieved the full tumor history of a historical clinic-based cohort of 1745 individuals with Lynch syndrome and calculated the standardized incidence ratio for all tumor types. MSI status, somatic second hit alterations, and immunohistochemistry-based MMR status were analyzed in 236 noncolorectal and nonendometrial malignant tumors.In individuals with Lynch syndrome MSI-H/dMMR occurred both in Lynch-spectrum and in non-Lynch-spectrum malignancies (85% vs 37%, P < .01). MSI-H/dMMR malignancies were found in nearly all non-Lynch-spectrum tumor types. Almost all breast carcinomas had medullary features, and most of them were MSI-H/dMMR. Breast carcinoma with medullary features were shown to be associated with Lynch syndrome (standardized incidence ratio = 38.8, 95% confidence interval = 16.7 to 76.5).In individuals with Lynch syndrome, MSI-H/dMMR occurs in more than one-half of the malignancies other than colorectal and endometrial carcinomas, including tumor types without increased incidence. The Lynch-spectrum tumors should be expanded to breast carcinomas with medullary features. All malignancies in patients with Lynch syndrome, independent of subtype, should be tested for MSI-H/dMMR in case therapy with immune checkpoint inhibitors is considered. Moreover, Lynch syndrome should be considered an underlying cause of all MSI-H/dMMR malignancies other than colorectal and endometrial carcinomas.
On the potentials of interaction breakdowns for HRI
Authors: Britta Wrede, Anna-Lisa Vollmer, Sören Krach
Journal: Behavioral and Brain Sciences (2023)

Abstract How do we switch between “playing along” and treating robots as technical agents? We propose interaction breakdowns to help solve this “social artifact puzzle”: Breaks cause changes from fluid interaction to explicit reasoning and interaction with the raw artifact. These changes are closely linked to understanding the technical architecture and could be used to design better human–robot interaction (HRI).
Errors in Author Affiliations, Table, and Figure 3
Journal: JAMA Psychiatry (2023)

Frederikke Hørdam Gronemann, PhD, Msc; Rikke Kart Jacobsen, Msc; Marie Kim Wium-Andersen, DMSc; Martin Balslev Jørgensen, DMSc; Merete Osler, DMSc; Terese Sara Høj Jørgensen, PhD, Msc
Specific causes of excess late mortality and association with modifiable risk factors among survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort
Authors: Stephanie B Dixon, Qi Liu, Eric J Chow, Kevin C Oeffinger, Paul C Nathan, Rebecca M Howell, Wendy M Leisenring, Matthew J Ehrhardt, Kirsten K Ness, Kevin R Krull, Ann C Mertens, Melissa M Hudson, Leslie L Robison, Yutaka Yasui, Gregory T Armstrong
Journal: The Lancet (2023)
Polypharmacy stewardship: a novel approach to tackle a major public health crisis
Authors: Ruth Daunt, Denis Curtin, Denis O'Mahony
Journal: The Lancet Healthy Longevity (2023)

With growing global concern regarding medication-related harm, WHO launched a global patient safety challenge, Medication Without Harm, in March, 2017. Multimorbidity, polypharmacy, and fragmented health care (ie, patients attending appointments with multiple physicians in various health-care settings) are key drivers of medication-related harm, which can result in negative functional outcomes, high rates of hospitalisation, and excess morbidity and mortality, particularly in patients with frailty older than 75 years. Some studies have examined the effect of medication stewardship interventions in older patient cohorts, but focused on a narrow spectrum of potentially adverse medication practices, with mixed results. In response to the WHO challenge, we propose the novel concept of broad-spectrum polypharmacy stewardship, a coordinated intervention designed to improve the management of multimorbidities, taking into account potentially inappropriate medications, potential prescribing omissions, drug-drug and drug-disease interactions, and prescribing cascades, aligning treatment regimens with the condition, prognosis, and preferences of the individual patient. Although the safety and efficacy of polypharmacy stewardship need to be tested with well designed clinical trials, we propose that this approach could minimise medication-related harm in older people with multimorbidities exposed to polypharmacy.
Differential serum neutralisation of omicron sublineages in patients receiving prophylaxis with tixagevimab–cilgavimab
Authors: Javier T Solera, Berta G Arbol, Victor H Ferreira, Alexandra Kurtesi, Queenie Hu, Matthew Ierullo, Adriana Valverde-Zuniga, Ismail Raslan, Asma Nasir, Clara Grizales, W Rod Hardy, Vathany Kulasingam, Anne-Claude Gingras, Atul Humar, Deepali Kumar
Journal: The Lancet Infectious Diseases (2023)
Diagnosis of fatty liver in children should occur in parallel to investigation for other causes of liver disease
Authors: Jake P Mann, Anita CE Vreugdenhil, Aglaia Zellos, Aleksander Krag, Anastasia Konidari, Anna Alisi, Bart Koot, Benno Kohlmaier, Christian A Hudert, Christos Tzivinikos, Cigdem Arikan, Corina Pienar, Deirdre Kelly, Eberhard Lurz, Elvira Verduci, Emanuele Nicastro, Emer Fitzpatrick, Giuseppe Indolfi, Giusy Ranucci, Henedina Antunes, Idoia Labayen, Irene Degrassi, Jan Melek, Jernej Brecelj, Jiri Bronsky, Judith Lubrecht, Kimberley Brook, Maria Fotoulaki, Maria Rogalidou, Marianne Samyn, Natalia Zavhorodnia, Norman Junge, Olha Zavhorodnia, Phil Newsome, Ruth DeBruyne, Sander Lefere, Stephenne Xavier, Thomas Berg, Tudor Lucian, Virginie Frings, Wojciech Jańczyk, Ulli Baumann
Journal: The Lancet. Gastroenterology & hepatology (2023)
Spleen fibroblastic reticular cell-derived acetylcholine promotes lipid metabolism to drive autoreactive B cell responses
Authors: Qin Zeng, Shuyi Wang, Mengyuan Li, Shuang Wang, Chaohuan Guo, Xinyuan Ruan, Ryu Watanabe, Yimei Lai, Yuefang Huang, Xiaoyu Yin, Chuanzhao Zhang, Binfeng Chen, Niansheng Yang, Hui Zhang
Journal: Cell Metabolism (2023)
Resolving the prefrontal mechanisms of adaptive cognitive behaviors: A cross-species perspective
Authors: Ileana L. Hanganu-Opatz, Thomas Klausberger, Torfi Sigurdsson, Andreas Nieder, Simon N. Jacob, Marlene Bartos, Jonas-Frederic Sauer, Daniel Durstewitz, Christian Leibold, Ilka Diester
Journal: Neuron (2023)
Oxytocin promotes prefrontal population activity via the PVN-PFC pathway to regulate pain
Authors: Yaling Liu, Anna Li, Chloe Bair-Marshall, Helen Xu, Hyun Jung Jee, Elaine Zhu, Mengqi Sun, Qiaosheng Zhang, Arthur Lefevre, Zhe Sage Chen, Valery Grinevich, Robert C. Froemke, Jing Wang
Journal: Neuron (2023)
Over and above frequency: Gamma oscillations as units of neural circuit operations
Authors: Antonio Fernandez-Ruiz, Anton Sirota, Vítor Lopes-dos-Santos, David Dupret
Journal: Neuron (2023)

Gamma oscillations (30-150 Hz) are widespread correlates of neural circuit functions.These network activity patterns have been described across multiple animal species, brain structures, and behaviors, and are usually identified based on their spectral peak frequency.Yet, despite intensive investigation, whether gamma oscillations implement causal mechanisms of specific brain functions or represent a general dynamic mode of neural circuit operation remains unclear.In this perspective, we review recent advances in the study of gamma oscillations toward a deeper understanding of their cellular mechanisms, neural pathways, and functional roles.We discuss that a given gamma rhythm does not per se implement any specific cognitive function but rather constitutes an activity motif reporting the cellular substrates, communication channels, and computational operations underlying information processing in its generating brain circuit.Accordingly, we propose shifting the attention from a frequency-based to a circuit-level definition of gamma oscillations.
IgE cross-inhibition between Ara h 1 and Ara h 2 is explained by complex formation of both major peanut allergens
Authors: Hans J.M. Warmenhoven, Luuk Hulsbos, Stephen C. Dreskin, Jaap H. Akkerdaas, Serge A. Versteeg, Ronald van Ree
Journal: Journal of Allergy and Clinical Immunology (2023)

Surprisingly, IgE cross-reactivity between the major peanut allergens Ara h 1, 2, and 3 has been reported despite very low sequence identities.We investigated the unexpected cross-reactivity between peanut major allergens.Cross-contamination of purified natural Ara h 1, 2, 3, and 6 was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot test, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and sandwich enzyme-linked immunosorbent assay (ELISA). IgE cross-reactivity was studied with sera of peanut-allergic patients (n = 43) by ELISA and ImmunoCAP inhibition using both intact natural and recombinant allergens and synthetic peptides representing postulated Ara h 1 and Ara h 2 cross-reactive epitopes.Both purified nAra h 1 and nAra h 3 were demonstrated to contain small but significant amounts of Ara h 2 and Ara h 6 (<1%) by sandwich ELISA, SDS-PAGE/Western blot analysis, and LC-MS/MS. IgE cross-inhibition between both 2S albumins and Ara h 1 and Ara h 3 was only observed when using natural purified allergens, not recombinant allergens or synthetic peptides. Apparent cross-reactivity was lost when purified nAra h 1 was pretreated under reducing conditions, suggesting that Ara h 2 and Ara h 6 contaminations may be covalently bound to Ara h 1 via disulfide interactions.True cross-reactivity of both peanut 2S albumins with Ara h 1 and Ara h 3 could not be demonstrated. Instead, cross-contamination with small quantities was shown to be sufficient to cause significant cross-inhibition that can be misinterpreted as molecular cross-reactivity. Diagnostic tests using purified nAra h 1 and nAra h 3 can overestimate their importance as major allergens as a result of the presence of contaminating 2S albumins, making recombinant Ara h 1 and Ara h 3 a preferred alternative.
Editorial Board
Authors: Zuhair Ballas, Iowa City, Iowa Deputy, David Huston, Rachel Miller, New York, N Associate, Andrea Apter, Leonard Philadelphia, Nashville Bacharier, Claus Bachert, Joshua Boyce, Javier Chinen, Raif Geha, Johann Gudjonsson, Ann Arbor, Mich Kenji Kabashima, Corinne Keet, Chapel Hill, Carole Ober, Wanda Phipatanakul, Harald Renz, Marburg Germany, Marc Rothenberg, Cincinnati Ohio, Hirohisa Saito, Stefan Vieths, Langen Germany, Stephan Weidinger
Journal: Journal of Allergy and Clinical Immunology (2023)
Comparative safety and effectiveness of TNF inhibitors, IL6 inhibitors and methotrexate for the treatment of immune checkpoint inhibitor-associated arthritis
Authors: Anne R Bass, Noha Abdel-Wahab, Pankti D Reid, Jeffrey A Sparks, Cassandra Calabrese, Deanna P Jannat-Khah, Nilasha Ghosh, Divya Rajesh, Carlos Andres Aude, Lydia Gedmintas, Lindsey MacFarlane, Senada Arabelovic, Adewunmi Falohun, Komal Mushtaq, Farah Al Haj, Adi Diab, Ami A Shah, Clifton O Bingham, Karmela Kim Chan, Laura C Cappelli
Journal: Annals of the Rheumatic Diseases (2023)

Objectives To compare the safety and effectiveness of biologic and conventional disease-modifying antirheumatic drugs (DMARDs) for immune checkpoint inhibitor-associated inflammatory arthritis (ICI-IA). Methods The retrospective multicentre observational study included patients with a diagnosis of ICI-IA treated with a tumour necrosis factor inhibitor (TNFi), interleukin-6 receptor inhibitor (IL6Ri) and/or methotrexate (MTX); patients with pre-existing autoimmune disease were excluded. The primary outcome was time to cancer progression from ICI initiation; the secondary outcome was time to arthritis control from DMARD initiation. Cox proportional hazard models were used to compare medication groups, adjusting for confounders. Results 147 patients were included (mean age 60.3 (SD 11.9) years, 66 (45%) women). ICI-IA treatment was TNFi in 33 (22%), IL6Ri 42 (29%) and MTX 72 (49%). After adjustment for time from ICI initiation to DMARD initiation, time to cancer progression was significantly shorter for TNFi compared with MTX (HR 3.27 (95% CI 1.21 to 8.84, p=0.019)) while the result for IL6Ri was HR 2.37 (95% CI 0.94 to 5.98, p=0.055). Time to arthritis control was faster for TNFi compared with MTX (HR 1.91 (95% CI 1.06 to 3.45, p=0.032)) while the result for IL6Ri was HR 1.66 (95% CI 0.93 to 2.97, p=0.089). A subset analysis in patients with melanoma gave similar results for both cancer progression and arthritis control. Conclusion The treatment of ICI-IA with a biologic DMARD is associated with more rapid arthritis control than with MTX, but may be associated with a shorter time to cancer progression.
Engineering second-generation TCR-T cells by site-specific integration of TRAF-binding motifs into the<i>CD247</i>locus
Authors: Sangjoon Lah, Segi Kim, In Kang, Hyojin Kim, Cedric Hupperetz, Hyuncheol Jung, Hyeong Ryeol Choi, Young-Ho Lee, Hyeon-Ki Jang, Sangsu Bae, Chan Hyuk Kim
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background The incorporation of co-stimulatory signaling domains into second-generation chimeric antigen receptors (CARs) significantly enhances the proliferation and persistence of CAR-T cells in vivo, leading to successful clinical outcomes. Methods To achieve such functional enhancement in transgenic T-cell receptor-engineered T-cell (TCR-T) therapy, we designed a second-generation TCR-T cell in which CD3ζ genes modified to contain the intracellular domain (ICD) of the 4-1BB receptor were selectively inserted into the CD247 locus. Results This modification enabled the simultaneous recruitment of key adaptor molecules for signals 1 and 2 on TCR engagement. However, the addition of full-length 4-1BB ICD unexpectedly impaired the expression and signaling of TCRs, leading to suboptimal antitumor activity of the resulting TCR-T cells in vivo. We found that the basic-rich motif (BRM) in the 4-1BB ICD was responsible for the undesirable outcomes, and that fusion of minimal tumor necrosis factor receptor-associated factor (TRAF)-binding motifs at the C-terminus of CD3ζ (zBB ΔBRM ) was sufficient to recruit TRAF2, the key adaptor molecule in 4-1BB signaling, while retaining the expression and proximal signaling of the transgenic TCR. Consequently, TCR-T cells expressing zBB ΔBRM exhibited improved persistence and expansion in vitro and in vivo, resulting in superior antitumor activity in a mouse xenograft model. Conclusions Our findings offer a promising strategy for improving the intracellular signaling of TCR-T cells and their application in treating solid tumors.